1. Field of the Invention
The disease Bluetongue is a systemic viral infection of ruminants, such as sheep and cattle. The Bluetongue virus (BTV) is transmitted by small biting flies and is known to occur in twenty serotypic variants that do not provide cross-protection immunologically.
The Bluetongue virus is the prototype orbivirus and is composed of ten double-stranded RNA genomic segments. Bluetongue virions have an inner capsid of five polypeptides and a diffuse non-enveloped outer layer containing two polypeptides. It is found that variable amino acid sequences in P2, the major surface polypeptide, are responsible for immunologic serotype specificity. A core protein, P7, is detected by the complement fixation assay and determines cross-reacting group specificity.
In the United States, the primary serotypes observed are 11 and 17, with serotypes 2, 10 and 13 being observed less frequently.
The first vaccine for BTV was an attenuated live virus vaccine, which has been utilized over forty years in South Africa. Other modified live virus Bluetongue vaccines have also been reported. These attenuated live virus vaccines induce teratogenic lesions in fetuses and may also result in the emergence of recombinant virus strains. There is, therefore, need for an effective vaccine against Bluetongue, which provides protection to an inoculated mammalian host, without the hazards observed with attenuated live Bluetongue virus.
2. Description of the Prior Art
Theiler, Vet. J. (1908) 64:600-607 describes an attenuated live Bluetongue virus vaccine. Kemeny and Drehle, Am. J. Vet. Res. (1961) 22:921-925 describe a tissue culture-propagated BTV for vaccine preparation. Alexander and Haig, Onderstepoort J. Vet. Res. (1951) 25:3-15 describe the use of attenuated BTV in the production of a polyvalent vaccine for sheep. Parker et al., Vet. Rec. (1975) 96:284-287 describe an inactivated vaccine against Bluetongue.
Isaacs et al., Biochemistry (1977) 16:1058-1064, describe the synthesis of several psoralen derivatives and their photoreactivity with double-stranded RNA. Hearst and Thiry, Nucleic Acids Research (1977) 4:1339-1347; Hanson et al., J. Gen. Virol. (1978) 40:345-358; and Talib and Banerjee, Virology (1982) 118:430-438, describe the photoreactivity of various psoralen derivatives with animal viruses. Hanson, in Medical Virology II, Proceedings of the 1982 International Symposium on Medical Virology, de la Maza and Peterson, eds., New York: Elsevier Biomedical, 1983, pp. 45-75, has cited unpublished data on the inactivation of Bluetongue virus utilizing psoralen photochemistry.